Using Genetic Tools to Dissect Neural Circuits for Social Communication

使用遗传工具剖析社交沟通的神经回路

• 批准号: 10152701
• 负责人: Richard D Mooney
• 金额: $ 51.39万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-11 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10152701
• 关键词: Acoustics; Adult; Affect; Brain; Calcium; Chemicals; Communication; Data; Disease; Electrophysiology (science); Female; Foundations; Future; Genetic; Human; Image; Impairment; Individual; Influentials; Link; Mammals; Maps; Measures; Medial; Mediating; Mental disorders; Methods; Midbrain structure; Monitor; Mus; Neurodevelopmental Disorder; Neurons; Pattern; Perception; Play; Prefrontal Cortex; Production; Research; Role; Schizophrenia; Signal Transduction; Social Environment; Social Functioning; Social Interaction; Social Work; Testing; Ultrasonics; autism spectrum disorder; behavior measurement; cortex mapping; genetic approach; imaging modality; in vivo calcium imaging; in vivo imaging; innovation; insight; male; midbrain central gray substance; mind control; mouse model; neural circuit; neuropsychiatric disorder; novel; optogenetics; relating to nervous system; response; skills; social; social attachment; social communication; social deficits; sound; stem; tool; virus genetics; vocalization

Project Summary An inability to form and maintain social bonds typifies a wide range of neuropsychiatric and neurodevelopmental disorders. These social deficits stem in large part from impaired expressive and receptive vocal communication skills. Surprisingly, exactly how vocal communication promotes social affiliation is not well understood, in part because the underlying neural circuits remain poorly described. Here we propose the use of a novel genetic approach to selectively tag neurons that are active during social encounters that elicit vocalizations. We will combine this innovative method with in vivo imaging, electrophysiology, chemical and optogenetic perturbations of neural activity, and behavioral measurements to identify neural circuits that facilitate expressive and receptive aspects of vocal communication in the service of social affiliation. In Aim 1, we will test the idea that a specific subpopulation of neurons in the midbrain periaqueductal gray (PAG) is required for male and female mice to produce vocalizations used during their social interactions. In Aim 2, we will manipulate the activity of these PAG neurons to suppress or augment vocalization, allowing us to test the idea that these vocalizations promote social affiliation. In Aim 3, we will test the idea that prefrontal cortical (PFC) neurons that provide input to PAG vocalization neurons are important in regulating vocalization as a function of social context. In Aim 4, we will either reversibly silence or image PFC neurons that provide input to the PAG to test the idea that they play a role in generating affiliative social responses in males and females listening to a vocalizing individual. These studies will identify the neurons and circuits that gate vocalization during social encounters and promote social affiliation in response to these acoustic signals. This research will also build the foundation for future studies that explore how these circuits are affected in mouse models of neuropsychiatric disorders characterized by social communication and affiliation deficits, such as autism spectrum disorder and schizophrenia.

项目摘要 无法形成和维持社会联系是一种广泛的神经精神疾病和 神经发育障碍这些社交缺陷在很大程度上源于表达和接受能力的受损 声音沟通技巧。令人惊讶的是，声音交流如何促进社会联系并不是 很好理解，部分原因是底层的神经回路仍然没有得到很好的描述。在这里，我们建议 使用一种新的遗传方法来选择性地标记在社会交往中活跃的神经元， 发声我们将联合收割机与体内成像、电生理学、化学和 神经活动的光遗传学扰动和行为测量，以识别 促进表达和接受方面的声音沟通服务的社会联系。在目标1中， 我们将测试中脑导水管周围灰质（PAG）中神经元的特定亚群的想法， 这是雄性和雌性小鼠在社会交往中发出声音所必需的。在目标2中， 将操纵这些PAG神经元的活动，以抑制或增强发声，使我们能够测试 认为这些发声促进了社会联系。在目标3中，我们将测试前额叶皮层 (PFC)向PAG发声神经元提供输入的神经元在调节发声中是重要的， 社会背景的作用。在目标4中，我们将可逆地沉默或成像PFC神经元，这些神经元提供输入， PAG测试的想法，他们发挥了作用，在产生亲和的社会反应，男性和女性 倾听一个人的声音这些研究将确定控制发声的神经元和回路 在社会交往中，并促进社会联系，以响应这些声音信号。这项研究将 也为未来的研究奠定了基础，这些研究探索了这些电路是如何在小鼠模型中受到影响的。 以社交和联系缺陷为特征的神经精神障碍，如自闭症 谱系障碍和精神分裂症。